In vitro, human skin cells can be converted to several other cell types by introducing, in excess, certain proteins which are naturally present in some human cell. As the skin cells progress through the cell cycle, they update these exogenous proteins which bind to the cell's DNA and orchestrate the structural and functional changes which alter the cell's identity. These binding proteins, transcription factors, are necessary for a variety of natural cellular functions and many of them have been characterized and used in cell type conversions.
Manually directed conversion between cell types outside of the natural cell progression, or reprogramming, was first demonstrated in 1989 by Harold Weintraub et al., who reprogrammed human skin cells into muscle cells by over-expressing one particular protein. In 2006, Shinya Yamanaka et al reprogrammed human skin cells to stem cells using the combination of four proteins. Since then a wide-variety of other cell type conversions have been discovered and confirmed in the laboratory setting. Together, these discoveries have given credence to the idea that any cell type may have the potential to be reprogrammed to any other cell type given the correct transcription factors, regardless of cell-type differentiation. All of these findings were based on a deep understanding of the function of each protein, the transcription profile of each cell type, and considerable trial and error, particularly in the case of Yamanaka.
In attempting to optimize the efficiency of the reprogramming process, and bypass time-intensive wetlab methods, a computational method has been developed for determining potentially useful transcription factors prior to testing.
This section provides background information related to the present disclosure which is not necessarily prior art.